Objective To study the relationship between genotype and phenotype of familial hypertrophic cardiomyopathy (HCM) by analyzing its pathogenic gene mutation site.Methods The exon and boarding introns in HCM-related genes were amplified by target exon trapping sequencing and tested in HCM patients and 200 volunteers by Sanger sequencing to identify the pathogenic mutations.Clinical manifestations,physical examinations,electrocardiography,echocardiography,cardiac MRI data were recorded.Results A missense mutation c.2389G＞A (A797L) was identified in 4 MYH7 gene carriers,a nonsense mutation c.G10306T (E3436X) was identified in 4 TTN gene carriers,a missense mutation c.196 G＞C was identified in 3 GLA gene cariers,which was located in No.2 exon of the GLA gene and resulted in glutamic acid (Glu) to glutamine (Gln) at amino acid residue 66.The onset time of HCM was earlier,the clinical manifestations were severer,the inerventricular septum was thicker and the left atrium was larger in MYH7,TTN and GLA gene carriers.Conclusion Mutation of MYH7 gene c.2389G＞A is a pathogenic mutation of HCM.The onset time of HCM is earlier and the phenotype is severer in patients carrying heterozygous mutations.%目的 对收集的肥厚型心肌病(hypertrophic cardiomyopathy)家系的致病基因进行突变位点分析,阐明基因型与临床表型的关系.方法 利用靶向外显子捕获测序的方法对肥厚型心肌病先证者的30个肥厚型心肌病相关的基因进行全外显子扩增和高通量测序,进一步通过Sanger测序法在该家系内及另选择200例健康志愿者进行验证,确定该家系患者的致病突变.对肥厚型心肌病的家系调查资料包括临床表现、体格检查、心电图及超声心动图或心脏核磁共振检测结果.结果 该家系12例有血缘关系的研究对象中4例携带MYH7基因c.G2389A杂合突变(A797L).4例携带TTN基因c.G10306T杂合无义变异(E3436X).3例携带GLA基因c.G196C杂合突变,该突变位点位于GLA基因的第2号外显子并使66位的谷氨酸变为谷氨酰胺.该家系先证者同时携带上述3种突变基因,先证者肥厚型心肌病发病早,临床症状重,彩色超声显示室间隔梭形肥厚(厚度为24 mm),心肌回声斑点状增强,心肌纹理排列紊乱,运动减弱,心脏核磁共振显示室间隔及毗邻前壁增厚,延迟强化室间隔心肌壁内可见轻度晕状强化.结论 MYH7基因c.G2389A突变可能是肥厚型心肌病的致病突变,携带复合突变的家系成员心肌病发病早、表型重.
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